The mechanisms of action of oligomeric proteins that participate in higher levels of organization will be studied by means of x-ray diffraction techniques. In particular, we propose to study the structure, function and regulation of multienzyme alpha-keto acid dehydrogenase complexes. The structure of the dihydrolipoyl transsuccinylase core of the alpha-ketoglutarate dehydrogenase will be determined and its mechanism of action studied. The composition and quaternary structure of a putative transacetylase-flavoprotein subcomplex of the pyruvate dehydrogenase complex will be studied at low resolution. Additional crystallographic studies of other components are also anticipated. These studies will not only provide valuable insight about the structure and function of the alpha-keto acid dehydrogenase systems but will also increase our general understanding of protein-protein interactions, self-assembly processes and the general advantages the cell derives from the specific ordering of its enzymes. In addition, we propose to complete work on the structure of an invertebrate hemoglobin homodimer to further delineate the relationships of vertebrate and invertebrate hemoglobins with respect to the evolution of functional domains at the subunit-interface.